[Challenges for Urologists in the Care of Patients with Lynch Syndrome: Example of A Patient with Muir-Torre Syndrome, A Subtype of Lynch Syndrome]. / Herausforderungen für den Urologen in der Betreuung von Patienten mit Lynch-Syndrom am Beispiel eines Patienten mit Muir Torre-Syndrom als Unterform des Lynch-Syndroms.

The Muir-Torre syndrome (MTS) is a subtype of the Lynch syndrome (hereditary nonpolyposis colorectal cancer). In addition to tumours typically related to LS, MTS is associated with tumours of the sebaceous gland or keratoacanthoma. MTS is mostly characterised by a mutation of MSH2. In contrast to LS-associated tumours carrying a mutation of MLH1, MSH6 or PMS2, the frequency of urological neoplasms seems to be higher in Lynch syndrome patients with MSH2 mutation. Urological implications for the care of patients with LS or MTS include the early diagnosis of a possible hereditary background in patients presenting with urothelial cancers at an atypically young age and potentially the surveillance of carriers of mutations with an increased risk for urothelial cancers like males harbouring a MSH2 mutation. We report on a patient with various types of LS-associated cancers and cancers without a known association with LS, who died from multifocal metastasis of urothelial cancer. This case report shows that close interdisciplinary cooperation is mandatory for the treatment of patients with complex diseases.

Pharmacogenetic predictors for EGFR-inhibitor-associated skin toxicity.

The aim of this study was to investigate pharmacogenetic determinants of skin rash associated with epidermal growth factor receptor (EGFR) inhibitor treatment. A total of 109 prospectively sampled cancer patients, receiving the first treatment with an EGFR inhibitor, were genotyped for functional EGFR polymorphisms and tagging variants in genes involved in receptor downstream signaling. Skin rash was absent in 26 (23.9%) patients and associated with shorter overall survival compared with patients presenting skin rash (P=0.005). The EGFR polymorphisms, 497G/A (P=0.008), and the haplotypes of the promoter variants, EGFR-216G/T and -191C/A (P=0.029), were associated with the appearance of skin rash. In addition, a common haplotype in the PIK3CA gene was associated with skin rash (P=0.045) and overall survival (P=0.009). In conclusion, genetic variation within the EGFR gene and its downstream signaling partner PIK3CA might predict EGFR-inhibitor-related skin rash.

[Pronounced pancytopenia with concomitant jaundice in a 66-year-old woman]. / Ausgeprägte Trizytopenie mit Ikterus bei einer 66-jährigen Patientin.

HISTORY AND ADMISSION FINDINGS: A previously healthy 66-year-old women presented with onset of general weakness, shortness of breath and significant weight loss. Due to appearance of jaundice, biliary obstruction had been ruled out by a CAT scan previous to the patients presentation in our practice. INVESTIGATIONS: The laboratory tests already arranged by the patients general practitioner showed a pronounced pancytopenia with megaloblastic anemia and hyperbilirubinemia. The bone marrow aspiration revealed a hypercellular bone marrow with megaloblastic erythropoiesis. The diagnosis of pernicious anemia was confirmed by the low cobalamin (vitamin B12) serum level and the presence of atrophic gastritis. TREATMENT: Pernicious anemia was treated with intramuscular injection of Cyanocobalamin (1000 µg) which resulted in an immediate reticulocytosis and a widely normalized blood cell count and bilirubin level four weeks after initiation of treatment. CONCLUSION: The differential diagnosis of megaloblastic anemia covers a wide spectrum of diseases with different etiology. This case report demonstrates an example of a pernicious anemia with atypical and foudroyant clinical course.

[Chemotherapy for colorectal carcinoma in the elderly]. / Chemotherapie kolorektaler Karzinome im Alter.

With nearly 50 % of all colorectal cancers being diagnosed in patients at the age of 70 or above colorectal cancer is a disease of the elderly. In an adjuvant setting, fit elderly patients can receive the same benefit from cytotoxic therapy as younger patients with an only slightly increased toxicity. In a palliative setting, the treatment of elderly patients with respect to clinical endpoints such as response, time to progression or overall survival is as effective as in their younger counterparts. In clinical studies, older patients are generally underrepresented and among the elderly patients involved in clinical studies there is a bias towards particularly fit patients. Therefore it is not possible to extrapolate the results of many randomized trials to all elderly patients. A Comprehensive Geriatric Assessment (CGA) should be applied to detect the diversities in the geriatric population. Based on this assessment elderly patients classified as suitable for chemotherapy should be enrolled into clinical trials for colorectal cancer.

Long-term seropositivity against Echinococcus multilocularis in an epidemiological follow-up study in southwestern Germany (Römerstein).

BACKGROUND: Out of 2,560 participants in an epidemiological survey of alveolar echinococcosis (AE) performed in 1996 in southwestern Germany, 47 participants had tested seropositive in one of two crude antigen screening ELISAs and were inconspicuous on hepatic ultrasound. PATIENTS AND METHODS: Out of these 47 seroreactors, 36 attended a follow-up examination 30 months after the primary examination, including ultrasound and serology with various Echinococcus multilocularis-specific antigens. RESULTS: No lesion suspicious for AE was detected in any participant. Serology showed only minor changes as compared to the earlier results. CONCLUSION: Persistent seropositivity without detectable hepatic lesions could be interpreted as an early sign of sonographically not yet detectable AE, immunity to E. multilocularis or unspecific serological reactivity. For seropositive and clinically inconspicuous inhabitants of areas endemic for AE follow-up examinations at intervals of 2-3 years seem to be adequate.

[Contrast enhanced power Doppler sonography: comparison of various administration forms of the ultrasound contrast agent Levovist]. / Kontrastverstärkte Power-Doppler-Sonographie: Vergleich verschiedener Applikationsformen des Ultraschallkontrastverstärkers Levovist.

PURPOSE: Objective of the present study was the comparison of various administration forms of the ultrasound contrast medium Levovist with regard to duration and intensity of contrast enhancement in patients with tumors of the liver or pancreas. PATIENTS AND METHODS: Seven patients with tumors of the liver or pancreas were examined prospectively using power Doppler sonography. Ultrasound contrast enhancement was achieved using Levovist (8 ml, 400 mg/ml) in three different administration forms: 1st as a bolus injection through the main channel, 2nd through the injection valve of an intravenous cannula, or 3rd as a continuous infusion. Semiquantitative evaluation of the degree of contrast enhancement over the course of the examination was conducted by three independent examiners. RESULTS: Levovist, administered by continuous infusion, resulted in a significantly longer average period of contrast enhancement (9:43 min (extratumoral), 7:34 min (intratumoral)) than did the same dosage administered as a bolus injection through the main channel (6:01 min (extratumoral), 4:54 min (intratumoral), p = 0.0156 (extratumoral); p = 0.0313 (intratumoral), but contrast intensity was decreased. Bolus injection through the injection valve of the i.v. cannula was associated with decreased duration and intensity of contrast enhancement compared with injection through the main channel. CONCLUSION: Compared with bolus injection, the continuous infusion of Levovist resulted in a significant prolongation of the duration but in a decreased intensity of contrast enhancement. Administration of Levovist through the injection valve does not result in optimal contrast enhancement and is therefore not recommended.

[The effect of ABO, Rhesus and Kell blood group antigens on gallstone prevalence. A sonographic study of 1030 blood donors]. / Einfluss von AB0-, Rhesus- und Kell-Blutgruppenantigenen auf die Gallensteinprävalenz. Eine sonographische Untersuchung an 1030 Blutspendern.

BACKGROUND AND OBJECTIVE: Besides generally accepted risk factors of the pathogenesis of gallstone disease such as age, obesity, female sex and high number of births, hereditary factors are held responsible for different prevalence rates. A number of studies dealt with the question of a correlation between the prevalence of gallstone disease and different blood groups. The Ulm Gall Bladder Stone Study represents the first sonographic prospective study regarding this issue. SUBJECTS AND METHODS: Unselected blood donors (n = 1030, 606 men, mean age 38.0 years, 424 women, mean age 34.1 years) were sonographically examined for presence of gallstones at the German Red Cross blood donor centre in Ulm. Besides AB0, Rhesus and Kell blood group anthropometric data of the test subjects were recorded by means of a semi-standardized interview. RESULTS: The prevalence of gallstone disease in all test subjects was 6.0%. Within the AB0 system the prevalence in subjects with blood group AB was highest (12.1%). The prevalence in Rh-positive and Rh-negative subjects was nearly identical (6.0 vs. 6.1%). Kell factor positive subjects suffered less from gallstone disease than Kell factor negative subjects (2.0 vs. 6.3%). None of these differences in prevalence were statistically significant. CONCLUSION: This study revealed no significant correlation between the distribution of the AB0, Rhesus and Kell blood group antigens and the prevalence of gallstone disease.

Prevalence of gallstones in sonographic surveys worldwide.

The use of diagnostic sonography allows determination of the prevalence of gallstones in a representative sample of the general population. The objective of this article is to review the reports of sonographically based studies of gallstone prevalence in the world literature. All available published epidemiologic studies on the prevalence of cholecystolithiasis as determined by diagnostic sonography are summarized. The sonographically based studies published to date confirm that there are significant regional differences in the prevalence of gallstones. Certain risk factors, notably age and heredity, are present worldwide.

[Prevalence of cholecystolithiasis in South Germany--an ultrasound study of 2,498 persons of a rural population]. / Prävalenz der Cholezystolithiasis in Süddeutschland--eine sonographische Untersuchung an 2.498 Personen einer ländlichen Bevölkerung.

Gallbladder stones represent one of the most common reason for morbidity in western industrial nations. There remains a paucity of exact information regarding the prevalence and risk factors for this disease entity in Germany. As part of a whole-community survey focusing on the prevalence of echinococcosis multilocularis conducted in a population in southwestern Germany (response rate: 66.6%), 2,560 subjects underwent an upper abdominal ultrasound examination at which the presence of gallbladder stones was ascertained. In each case, upper abdominal sonography was performed following completion of a standardized interview. In 62 subjects, the gallbladder could not be adequately visualized due to an insufficient fasting period; the remaining 2,498 subjects (1,326 females, age 38.9 +/- 19.9 years; 1,172 males, age 37.7 +/- 18.8 years) were included in the study collective. Gallbladder stones (sonographically visualized gallbladder stones or history of cholecystectomy for cholecystolithiasis) were found in 196 participants (7.8%; 139 females [10.5%] versus 57 males [4.9%]). Statistical treatment of the data using multiple logistical regression techniques revealed a significant influence of the variables age, gender, body mass index (BMI) and positive family history on the development of gallbladder stones. The prevalence of gallbladder stones in the present study population is lower than figures reported for a study in Brandenburg and at 7.8% is rather low in comparison with other European studies. One explanation may be the low average age of study participants, almost 50% of whom were less than 35 years. Besides age, subjects' gender, BMI and positive family history were identified as significant risk factors.

Gallstone prevalence in Germany: the Ulm Gallbladder Stone Study.

The Ulm Gallbladder Stone Study is the first ultrasound-based epidemiologic survey of cholecystolithiasis in the former West Germany. A study population of 1116 blood donors (656 men, age 38.0 +/- 12.0 years; 460 women, age 34.1 +/- 11.2 years) at the Central Blood Bank of the German Red Cross in Ulm was examined between April 1994 and February 1995. Based on age, subjects were assigned to one of four groups (18-30, 31-40, 41-50, and 51-65 years). Following a structured interview of each study subject, an ultrasound examination was carried out and a blood sample obtained for laboratory study. Overall, 6.0% (95% (95% CI: 4.8%-7.6%) of all study subjects (5.8% of the men and 6.3% of the women) exhibited evidence of current or past gallbladder disease (cholelithiasis or history of cholecystectomy). The prevalence of gallbladder disease correlated positively with age, reaching a maximum of 13.7% (9.5-20.0) in the 51- to 65-year-old age group, and also correlated as with body mass index (BMI). Female subjects with previous full-term pregnancies showed a higher prevalence of cholelithiasis, but this difference was not statistically significant for age-adjusted analysis. Subjects with a family history of cholelithiasis were found to suffer from gallstones in 11.5% (8.0-16.7) of cases compared with 4.6% (3.4%-6.3%) of subjects without such family history. Autopsy studies conducted in Germany have shown the prevalence of gallstones to be about 13.1% in men and 33.8% in women. Our sonographic data are relatively low in comparison. This may be due, in part, to the specific selection characteristics inherent in retrospective autopsy studies, such as age distribution and the presence of other pathologic factors associated with increased risk for cholelithiasis. The Ulm data rank in the lower third of the prevalence range reported for European sonographic studies to date. Age, positive family history, and increased BMI all correlated positively with the prevalence of gallbladder disease (P < 0.05). For the study population as a whole, there was no gender-specific increased risk for the development of gallstones.

Gallstone prevalence in relation to smoking, alcohol, coffee consumption, and nutrition. The Ulm Gallstone Study.

BACKGROUND: Besides considering well-known risk factors for the development of gallbladder stones, such as age, sex, fecundity, and hereditary predisposition, efforts at prevention have focused increasingly on other factors, such as nicotine, alcohol, and caffeine consumption, as well as general nutrition, which may be modified. METHODS: A total of 1116 blood donors were examined between April 1994 and February 1995 in the central blood bank of the German Red Cross in Ulm, Germany. Each subject received a questionnaire and underwent to an upper abdominal ultrasound examination. RESULTS: Gallbladder stone disease (current cholecystolithiasis and history of cholecystectomy) was detailed in 5.8% of the men and 6.3% of the women. Neither regularity nor number of daily meals correlated with the frequency of gallstone disease. Vegetarians (n = 48), as a group, were not found to have gallstones. In relation to the consumption of alcohol, tobacco, or caffeine higher prevalence of cholecystolithiasis was found only in heavy drinkers of coffee (P = 0.051; odds ratio (OR), 1.083; 95% confidence interval (CI), 0.999, 1.174). CONCLUSION: Results of the present study do not show a definite relationship between nutritional factors and the consumption of alcohol, tobacco, or caffeine and an increased prevalence of gallbladder stone disease.